左心交感神经切除术治疗长QT综合征的远期疗效

The long-term efficacy of left cardiac sympathetic denervation in long QT syndrome

目的观察左心交感神经切除术(LCSD)对我国药物治疗无效或不耐受的长QT综合征(LQTS)患者的远期疗效和安全性。方法本研究为回顾性队列研究,研究对象来自1999年11月至2012年11月期间入选中国离子通道病全国注册研究的193例LQTS患者,本研究选取其中药物治疗无效或不耐受,在北京大学人民医院或北京同仁医院进行LCSD手术的28例患者。QTc>550 ms或首次发病≤1岁或携带高危突变的为高危组(n=13),QTc介于500~550 ms且首次发病>1岁、不携带高危突变的为中危组(n=10),QTc<500 ms且首次发病>1岁、不携带高危突变的为低危组(n=5)。对3组患者行传统或经胸腔镜(VATS)LCSD手术。随访至术后20年,收集术前基线资料及术后1年和末次随访的数据,随访内容包括心电图数据采集、心脏事件发作情况、手术相关并发症。分别对不同危险分层以及不同基因分型患者术后无心脏事件发生的生存率进行Kaplan-Meier生存分析。结果28例行LCSD手术的LQTS患者中,女性23例(82.1%),手术时年龄20.5(15.0,37.5)岁,传统术式11例(39.3%),VATS-LCSD术式17例(60.7%)。19例(67.9%)患者基因检测结果阳性,包括4例LQT1、12例LQT2、1例LQT1/LQT2混合型、2例Jervell-Lange-Nielsen(JLN)综合征。术后随访189.3(138.7,204.9)个月,3组间随访时间差异无统计学意义(P>0.05)。失访率为10.7%(3/28),失访3例均在中危组。随访期间1例(4.0%)患者出现Horner综合征(在高危组),3例(12.0%)患者发生心脏性猝死(均在高危组),12例(48.0%)患者再发晕厥(低危组2例,中危组3例,高危组7例)。与术前相比,LCSD术后1年与末次随访时患者的心脏事件人年均发作次数降低[术后1年(0.2±0.1)次,末次随访(0.5±0.8)次,术前(3.5±3.3)次,P<0.001]。末次随访时QTc值较术前缩短[(489.0±40.1)ms比(545.7±51.2)ms,P<0.001]。在术前基础QTc值≥500 ms且完成随访的20例患者中,有11例(55.0%)在末次随访时QTc值缩短至<500 ms。无任何心脏事件的远期生存率在低、中、高危组依次降低,差异有统计学意义(χ^(2)=7.24,log-rank P=0.026)。LQT1、LQT2与未定型患者无心脏事件的远期生存率差异无统计学意义(χ^(2)=5.20,log-rank P>0.05)。结论LQTS患者LCSD术后远期心脏事件发作减少、QTc间期缩短。LCSD手术对于药物治疗无效或不耐受的LQTS患者的远期疗效可靠、安全,但高危患者术后仍有发生猝死的风险,应加强随访,积极采取其他预防措施。

Objective To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD)for long QT syndrome(LQTS)patients with either recurrence on drug therapy intolerance/refusal.Methods This study was a retrospective cohort study.The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012.This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People′s Hospital or Beijing Tongren Hospital.The patients were allocated into 3 groups:high-risk group(n=13,baseline QTc≥550 ms or symptomatic in the first year of life or highly malignant genetics);intermediate-risk group(n=10,500 ms≤baseline QTc<550 ms,symptomatic after the first year and without highly malignant genetics);low-risk group(n=5,baseline QTc<500 ms,symptomatic after the first year and without highly malignant genetics).LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery(VATS).Patients were regularly followed up until 20 years after the surgery.Data were collected before and 1 year after surgery and at the last follow-up.Patients′electrocardiograph(ECG),cardiac events and surgery-related complications were recorded.Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes.Results A total of 28 LQTS patients,aged 20.5(15.0,37.5)and underwent LCSD surgery,were enrolled in this study,including 23(82.1%)women.There were 11(39.3%)patients treated with traditional approach while 17(60.7%)with VATS-LCSD.There were 19(67.9%)patients had positive genetic test results,including 4 LQT1,12 LQT2,1 LQT1/LQT2 mixed type,and 2 Jervell-Lange-Nielsen(JLN)syndrome.The median follow-up period was 189.3(138.7,204.9)months.The dropout rate was 10.7%(3/28)while 3 patients in the intermediate-risk group were lost to follow-up.Horner syndrome occurred in 1 patient(in the high-risk group).Sudden cardiac deaths were observed in 3(12.0%)patients(all in the high-risk group),and 12 patients(48.0%)had syncope recurrences(2 in low-risk group,3 in intermediate-risk group and 7 in high-risk group).A significant reduction in the mean yearly episodes of cardiac events was observed,from(3.5±3.3)before LCSD to(0.2±0.1)at one year after LCSD and(0.5±0.8)at last follow up(P<0.001).The mean QTc was shortened from(545.7±51.2)ms before the surgery to(489.0±40.1)ms at the last follow-up(P<0.001).Among the 20 patients with basic QTc≥500 ms and completing the follow-up,the QTc intervals of 11(55.0%)patients were shortened to below 500 ms.The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-,intermediate-and high-risk groups,and the difference was statistically significant(χ^(2)=7.24,log-rank P=0.026).No difference was found in the event free survival rates among LQT1,LQT2 and undefined gene patients(χ^(2)=5.20,log-rank P>0.05).Conclusions LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up.LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy.However,high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.